THYROTROPIN-RELEASING-HORMONE (TRH) UPTAKE IN INTESTINAL BRUSH-BORDER MEMBRANE-VESICLES - COMPARISON WITH PROTON-COUPLED DIPEPTIDE AND NA+-COUPLED GLUCOSE-TRANSPORT

被引:13
作者
THWAITES, DT
SIMMONS, NL
HIRST, BH
机构
[1] UNIV NEWCASTLE UPON TYNE,SCH MED,GASTROINTESTINAL DRUG DELIVERY RES CTR,NEWCASTLE TYNE NE2 4HH,ENGLAND
[2] UNIV NEWCASTLE UPON TYNE,SCH MED,DEPT PHYSIOL SCI,NEWCASTLE TYNE NE2 4HH,ENGLAND
关键词
THYROTROPIN-RELEASING HORMONE (TRH); INTESTINAL ABSORPTION; BRUSH-BORDER MEMBRANE; MEMBRANE VESICLES; PEPTIDE TRANSPORT; DIPEPTIDE TRANSPORT; H+-COUPLED DIPEPTIDE TRANSPORT;
D O I
10.1023/A:1018995313180
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The mechanism of thyrotropin-releasing hormone (pGlu-His-Pro-NH2; TRH) uptake across the luminal membrane of intestinal enterocytes was investigated using brush-border membrane vesicles (BBMV) from rabbit duodenum and jejunum and rat upper small intestine. [C-14]Glucose accumulated within the intestinal vesicles (at 10 sec), in the presence of an inwardly directed Na+ gradient, 7- to 14-fold higher than equilibrium values (65 min). The vesicles also accumulated the dipeptide [C-14]Gly-Sar. Dipeptide uptake was greatest in the presence of both an inwardly directed proton gradient and an inside negative membrane potential. The H+-dependent Gly-Sar transport was not affected by the presence of an excess (46-fold) of cold TRH. In contrast to the observations with glucose and Gly-Sar, the uptake of [H-3]TRH after 10 or 60 sec (in each of the vesicle preparations) was not enhanced by either Na+ or H+ gradient conditions. The absence of vesicular accumulation of TRH was not due to peptide hydrolysis. For example, after a 60-sec incubation with rabbit jejunal BBMV no degradation of the tripeptide was evident. After 65 min, 69% of [H-3]TRH had undergone degradation, by deamidation, to form TRH-OH. These studies provide no evidence for the oral absorption of TRH by a Na+- or H+-dependent carrier system in the brush-border membrane. Previous observations of TRH absorption in vivo may be accounted for by passive absorption of the peptide combined with its relative resistance to luminal hydrolysis.
引用
收藏
页码:667 / 673
页数:7
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